磁共振评价磁探针标记的骨髓单个核及骨髓间充质干细胞移植治疗猪急性心肌梗死的疗效  

Therapeutic effects of magnetically labeled mononuclear and mesenchymal stem cells transplantation in a swine myocardial infarction model assessed by magnetic resonance imaging

作　　者：祁春梅[1] 马根山[1] 刘乃丰[1] 陈忠[1] 沈成兴[1] 刘孝钧[1] 胡耀鹏[1] 苏亚民[1] 李璇[1] 张晓黎[1] 滕皋军[1] 居胜红[1] 

机构地区：[1]东南大学附属中大医院心血管病研究所,南京210009

出　　处：《中华心血管病杂志》2008年第11期1004-1008,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30570743）

摘　　要：目的骨髓单个核细胞（BM-MNC）及骨髓间质干细胞（MSC）经磁探针标记后，应用磁共振成像（MRI）观察磁探针标记的BM-MNC（MR-MNC）及MSC（MR-MSC）治疗猪急性心肌梗死（AMI）的疗效。方法24头小型家猪经皮冠状动脉介入法成功制备AMI模型19头，随机分为MR—MSC组（n=7）、MR．MNC组（n=6）和AMI对照组（n=6），分别经冠状动脉途径植入MR—MSC、MR—MNC（细胞总数1×10^7）和含菲立磁标记物的磷酸盐缓冲液，MRI示踪移植细胞并观察8周后不同细胞类型移植对梗死心肌面积及心功能的影响，最后行组织学检查鉴定移植细胞及其功能。结果MRI示MR—MSC组、MR—MNC组均见呈低信号的标记细胞归巢至呈高信号的梗死心肌区周边或梗死心肌内。与移植前相比，8周后MRI测定梗死心肌面积在标记细胞移植组均明显缩小（MR—MSC组8．5％±0．5％比24．7％±3．1％，P〈0．05；MR—MNC组12．3％±1．5％比26．1％±1．5％，P〈0．05）；左室射血分数（LVEF）均有明显提高（MR—MSC组56．9％±1．3％比40．7％±2．0％，P〈0．05：MR—MNC组52．8％±1．4％比41．9％±3．3％，P〈0．05），但MR—MSC组LVEF改善程度优于MR—MNC组（16．2％±1．2％比10．9％±3．0％，P〈0．05）。普鲁士蓝染色证实标记细胞分布与MRI所见低信号区分布基本一致。Westernblot分析显示心肌再生指标肌球蛋白重链表达在MR—MSC组（100．3±5．5）及MR—MNC组（95．5±4．2）均高于AMI对照组（75．7±5．7）；心肌特异性肌钙蛋白T在MR—MSC组（124．0±5．8）及MR—MNC组（118．d±4．4）均高于AMI组（93．3±3．9）；心肌重构指标基质金属蛋白酶2（MMP2）／MMP抑制剂1（TIMP1）在MR—MSC组（0．6±0．1）及MR—MNC组（0．6±0．1）低于AMI对照组（4．2±0．2）。结论MR—MSC及MR—MNC可在体分化成表达心肌特异性蛋白的心肌样细胞，延缓心室重构，缩小梗Objective To evaluate the therapeutic effects of magnetically labeled mononuclear stem cells （MR-MNC） and mesenchymal stem cells （MR-MSC） transplantation in a swine acute myocardial infarction （AMI） model by MR imaging. Methods AMI model was established in swines by balloon occlusion of the left anterior descending coronary artery, 107 autologous MR-MSC （n = 7）, MR-MNC （n = 6 ） or PBS （ n = 6） were delivered via intracoronary infusion within I week after AMI [ （4. 8± 1.3 ） days ]. Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI. at 1 and 8 weeks post AMI. Results Magnetically labeled stem cells could be identified in the egion of AM1 by cardiac MR imaging. Eight weeks post transplantation, infarct size was significantly reduced in MR-MSC transplantation group （8.5% ±0. 5% vs. 24. 7%±3. 1%, P 〈 0. 05） and in MR-MNC transplantation （12.3%±1.5% vs. 26. 1% ± 1.5%, P 〈0.05） while infarct size remained unchanged in PBS group （P 〉0. 05） compared to values at 1 week post AMI, left ventricular ejection fraction （LVEF） was also significantly higher in MR-MSC transplantation group （56. 9% ±1.3 % vs. 40. 7%± 2.0%, P 〈 0. 05）and MR-MNC transplantation group（52. 8%± 1.4% vs. 41.9% ±3.3% , P 〈0.05） compared to LVEF at 1 week post AMI. LVEF increase was more significant in swines received MR-MSC transplantation than MR- MNC transplantation（ 16. 2% ±1. 2% vs. 10. 9%± 3.0% , P 〈 0. 05 ）. Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI. Western blot analysis demonstrated that cardiac expressions of myosin heavy chain （MHC） in MR-MSC group（ 100. 3 ± 5.5） and in MR-MNCs group （95.5±4. 2） were significantly higher than that in PBS group（75.7±5.7, P 〈0. 05）, myocardial troponin T （cTNT） expression in MR-MSC group （ 124. 0 ± 5.8 ） and MR-MNC group （ 118.4 ±4. 4 ） were also significantly higher than in PBS group （ 93.3 ± 3

关 键 词：心肌梗死 干细胞移植 磁共振成像 

分 类 号：R686[医药卫生—骨科学]